DESCRIPTION (Adapted from applicant's description): The candidate is a neonatology sub specialist in the field of pediatrics who has sought to develop a career in academic medicine since the outset of his pediatric training. The goal during this period will be to generate more skills necessary to enable the candidate to become a productive independent investigator. Recently in mice, the investigators have generated a series of mutations at the Fgf8 gene locus utilizing transgenic cre and Flp recombinase technology. Using this strategy they have created a null allele, a hypomorphic allele as well as an allele of Fgf8 that can be used in tissue specific gene elimination experiments. The experiments proposed are designed to examine the role of Fgf8 in LR axis determination and cardiac development. Particular attention will be paid to interactions between Fgf8 and Tgf-beta family members in the generation of LR asymmetry and to define the range of abnormalities seen in the compound heterozygous mutants. Experiments will be performed to analyze this phenotype and the molecular pathways involved in the generation of LR asymmetry and cardiac defects associated with abnormalities of LR axis determination. These cardiac defects include transposition of the great vessels, the most common congenital cyanotic heart disease in humans.